In many different medical settings, it would be advantageous to be able to detect changes in bodily fluids as they occurred in a noninvasive manner. For example, it is often critical to monitor intracranial changes in fluid in an intensive care unit patient. Standard of care for these patients includes invasive monitors that require drilling a hole in the cranium and inserting a probe such as an intracranial pressure (ICP) monitor, or microdialysis or “licox” probes for measuring chemical changes to the fluids in the brain. No noninvasive measurement techniques are currently commercially available for detecting cerebral fluid changes such as would occur with bleeding or edema, and many brain injuries are not severe enough to warrant drilling a hole in the cranium for invasive monitoring. Thus, for many patients with brain injury, there is no continuous monitoring technology available to alert clinical staff when there is a potentially harmful increase in edema or bleeding. Instead, these patients are typically observed by nursing staff, employing a clinical neurological examination, and it is not until increased fluid in the brain causes observable brain function impairment that the physicians or nurses can react. In other words, there is no way currently available for monitoring intracranial fluid changes themselves, and thus the ability to compensate for such changes is limited.
MIPS has been previously proposed for diagnosis of brain fluid abnormalities. Patents have been awarded for proposed devices, and promising scientific studies of prototype devices are described in the literature. For example, Rubinsky et al. described the use of MIPS for this purpose in U.S. Pat. Nos. 7,638,341, 7,910,374 and 8,101,421, the disclosures of which are hereby incorporated in their entirety herein (referred to herein as the “Rubinsky Patents”). However, no practical, mass-produced medical device based MIPS technology has yet emerged to provide clinicians specializing in brain treatment or other areas of medicine the promised benefits of such a device.
It was first postulated by Albert Einstein that the velocity of the transit of electromagnetic radiation in a vacuum is equal to the inverse of the square root of the product of magnetic permeability and electric permittivity. This formula yields the well-known value of the speed of light of approximately 3×108 meters/second. The finite time required for an electromagnetic field to propagate through a medium, however, results in a time delay, which is manifested as a phase shift (e.g., an offset or a delay) between a field emitted from a transmitter as compared with the field as sensed at a receiver. In other words, electromagnetic fields typically propagate fastest in a vacuum, and propagate slower if any matter or medium is present between the transmitter and the receiver. The amount of slowing is inversely proportional to the square root of the product of the relative permeability and relative permittivity of the medium.
The material makeup of biological materials is almost entirely non-magnetic, with a relative permeability of approximately 1. The variation in the time delay/phase shift through biological materials may therefore be mainly dependent on the average relative permittivity along the path through which the electromagnetic field passes. Relative permittivity varies for various tissue types and body fluids. The permittivity of the biological materials may also depend on the frequency of a time-varying electromagnetic field and may depend on the ambient temperature. The relative permittivity of body fluids is higher than most brain tissues, and thus, changes in fluid levels in the brain may have a relatively large effect on the overall phase shift of electromagnetic fields as they propagate through a brain or other medium.
For radiofrequency (“RF”) frequencies below about 200 MHz, the distance between opposing sides of the brain is less than one wavelength for normally propagating transverse electromagnetic waves. This is known as the near field, and in this region the electromagnetic waves are not fully formed. For this near field magnetic field propagation case, the propagation time and phase change is predominately determined by the loss factor of the tissues and liquids in the path rather than their relative permittivity. The loss factor is a function of the imaginary portion of the complex permittivity and the conductivity. The physical mechanism for dissipation of energy is the constant realignment of polarized molecules to the changing field polarity. Therefore the loss factor for a given substance is largely dependent on its ionic content. The ionic content of brain tissue and brain liquids is different for each substance. When combined with variations in relative permittivity, the various biological tissues and liquids in the brain display unique phase signatures when looking at phase changes for both the lower frequency near field propagation and higher frequency normal propagation cases. Because of the major difference in the physics that causes the phase delay, a multi-spectral measurement using RF frequencies both below and above 200 MHz allows characterization of not only the fractional amount of liquid in the brain, but sub-classifications of the exact nature of the liquid content such as the fractions of blood, cerebrospinal fluid (CSF), or the other liquids that accumulate in the cerebral cavity due to hemorrhaging or edema.
Again, despite research into use of MIPS for diagnosis of fluid changes in the body, no practical medical device based MIPS technology for doing so currently exists. A strong need exists for such technology. Ideally, a medical device solution would provide a MIPS system with improved performance, usability and manufacturability, such that it could be used for noninvasive fluid change detection in the brain and/or other areas of the body. At least some of these objectives will be addressed by the embodiments described herein.